The present invention is directed to the field of closures and devices using such closures, particularly testing devices for testing for analytes of biological interest.
Various closure devices are known in the art for closing test devices and require a flap or cover to be closed over a base portion of the test device. One simple example is a transfer adhesive that is applied to the base and covered with a peelable tape. The tape is removed and the flap is then pressed against and retained by the adhesive. Typically, however, the adhesive will not thereafter release the flap, so that the flap may not be again opened without destroying the transfer adhesive closure. Although resealable adhesives do exist, these adhesives are typically not strong enough for use in such devices.
If the flap is to be closed more than once, previously known closure techniques include peelable adhesives carried by a length of tape that is applied over the flap and base. The tape may be peeled back to open the flap and then reapplied to reclose the flap. Additional examples of closure techniques includes hook-and-loop fasteners and snap fasteners, where one element of such a fastener is affixed to the flap and the other element is affixed to the base of the device.
These alternatives, however, can be relatively expensive to manufacture, particularly where the elements of hook-and-loop or snap fasteners must be fixed to the flap and base of the device. Further, these closure techniques result in the device being secured at only one point or at most several discrete points between the flap and the base of the device. This can be a particular disadvantage in test devices that require a closing force to be evenly applied between the flap and the base of the device.
Among the many such devices that are useful for detection or determination of analytes, particularly analytes of biological interest, are chromatographic assay systems, particularly chromatographic assay systems that employ opposable components to transfer fluid from one element to another. Such assay systems are becoming of increasing importance.
Among the analytes frequently assayed with such systems are:
(1) hormones, such as human chorionic gonadotropin (hCG), frequently assayed as a marker of human pregnancy, as well as luteinizing hormone (LH), thyroid stimulating hormone (TSH), and follicle stimulating hormone (FSH); PA1 (2) antigens, particularly antigens specific to bacterial, viral, and protozoan pathogens, such as Streptococcus, hepatitis virus, and Giardia; PA1 (3) antibodies, particularly antibodies induced as a result of infection with pathogens, such as antibodies to the bacterium Helicobacter pylori and to human immunodeficiency virus (HIV); PA1 (4) other proteins, such hemoglobin, frequently assayed in determinations of fecal occult blood, an early indicator of gastrointestinal disorder, such as colon cancer; PA1 (5) enzymes, such as aspartate aminotransferase, lactate dehydrogenase, alkaline phosphatase, and glutamate dehydrogenase, frequently assayed as indicators of physiological function and tissue damage; PA1 (6) drugs, both therapeutic drugs, such as antibiotics, tranquilizers, and anticonvulsants, and illegal drugs of abuse, such as cocaine, heroine, amphetamines, and marijuana; and PA1 (7) vitamins. PA1 (1) a base member; PA1 (2) a cover member; PA1 (3) a fixed member fixed to the base member, the fixed member having an undercut edge; PA1 (4) a hinge between the base member and the cover member; PA1 (5) a testing element fixed to at least one of the base member or the cover member; and PA1 (6) closure means comprising an interrupted beveled edge on the cover member, the interrupted beveled edge being supplementary to the undercut edge and being adapted to be received and retained in a closed position with the undercut edge of the fixed member in a edge-to-edge engagement. PA1 (1) a base member; PA1 (2) a cover member; PA1 (3) fixed members fixed to the base member, each fixed member having an undercut edge; PA1 (4) a hinge between the base member and the cover member; PA1 (5) a testing element fixed to at least one of the base member or the cover member; and PA1 (6) closure means comprising interrupted beveled edges on the cover member, the beveled edges being supplementary to the undercut edges and being adapted to be received and retained in a closed position with the undercut edges of the fixed member in an edge-to-edge engagement. PA1 (1) a base member; PA1 (2) a cover member having an interrupted beveled edge; PA1 (3) a fixed member fixed to the base member, the fixed member having an undercut edge being supplementary to the beveled edge; PA1 (4) a hinge between the base member and the cover member, wherein closure of the cover member on the base member effects engagement of the beveled edge with the undercut edge of the fixed member, the interrupted beveled edge being adapted to be received and retained in a closed position in an edge-to-edge engagement with the undercut edge of the fixed member; and PA1 (5) a testing element fixed to the base member and a testing element fixed to the cover member, the members being in operable contact when the cover member and the base member are closed. PA1 (1) a base member; PA1 (2) a cover member having interrupted beveled edges; PA1 (3) fixed members fixed to the base member, the fixed members having undercut edges, the undercut edges being supplementary to the interrupted beveled edges such that in a closed position of cover member and base member the interrupted beveled edges and the undercut edges are in edge-to-edge alignment; PA1 (4) a hinge between the base member and the cover member; and PA1 (5) a testing element fixed to the base member and a testing element fixed to the cover member, the testing elements being in operable contact when the cover member and the base member are closed. PA1 (1) a base member; PA1 (2) a cover member; PA1 (3) a fixed member fixed to the base member, the fixed member having an undercut edge; PA1 (4) a hinge between the base member and the cover member; PA1 (5) a testing element fixed to the base member and a testing element fixed to the cover member, at least one of the testing elements including an elongated chromatographic medium, and wherein one of the testing elements is arranged for receiving fluid and for transferring fluid to the testing element having the chromatographic medium, whereby the fluid is arranged to traverse along the chromatographic medium along a defined flow path; and PA1 (6) closure means comprising an interrupted beveled edge on the cover member, the beveled edge being supplementary to the undercut edge and being adapted to be received and retained in a closed position with the undercut edge of the fixed member in an edge-to-edge engagement. PA1 (1) a base member; PA1 (2) a cover member; PA1 (3) fixed members fixed to the base member, each fixed member having an undercut edge; PA1 (4) a hinge between the base member and the cover member; PA1 (5) a testing element fixed to the base member and a testing element fixed to the cover member, at least one of the testing elements including an elongated chromatographic medium, and wherein one of the testing elements is arranged for receiving fluid and for transferring the fluid to the testing element having the chromatographic medium, whereby the fluid is arranged to traverse along the chromatographic medium along a defined flow path; and PA1 (6) closure means comprising interrupted beveled edges on the cover member, the interrupted beveled edge being supplementary to the undercut edges and being adapted to be received and retained in a closed position with the undercut edges of the fixed members in an edge-to-edge engagement. PA1 (1) a base member; PA1 (2) a cover member having an interrupted beveled edge, the interrupted beveled edge including an exposed line of engagement; PA1 (3) a fixed member fixed to the base member, the fixed member having an undercut edge being supplementary to the interrupted beveled edge and including an exposed line of engagement; PA1 (4) a hinge between the base member and the cover member; closure of the cover member on the base member effecting engagement of the interrupted beveled edge with the undercut edge, the interrupted beveled edge being adapted to be received and retained in a closed position in an edge-to-edge engagement with the undercut edge of the fixed member. In this embodiment, the base member, the cover member and fixed member are formed of a sufficiently rigid material to minimize bowing on the closure thereby to ensure that its sample for testing and the testing element come into operable contact for effecting a test, and that a force is distributed substantially evenly over the cover member and thereby further ensuring that, together with the hinge between the base member and the cover member, and with the closure means, the closure force is substantially equally distributed along the length of the closure means. The beveled edge is interrupted with at least one uncut bridge region to increase the force required to separate the base member and cover member. PA1 (1) a base member; PA1 (2) a cover member having interrupted beveled edges, the interrupted beveled edges including exposed lines of engagement; PA1 (3) fixed members fixed to the base member, the fixed members having undercut edges, the undercut edges being supplementary to the interrupted beveled edges and including exposed lines of engagement; PA1 (4) a hinge between the base member and the cover member; and PA1 (5) a testing element fixed to the base member and a testing element fixed to the cover member, at least one of the testing elements being arranged for receiving fluid and for transferring fluid to the other testing element; closure of the cover member on the base member effecting engagement of the interrupted beveled edges to be received and retained in edge-to-edge contact in the closed position with the undercut edges of the fixed members and the exposed lines of engagement of the beveled edges and the undercut edges respectively being substantially flush to the fixed members and the cover member.
Such chromatographic systems are frequently used by physicians and medical technicians for rapid in-office diagnosis or therapeutic monitoring of a variety of conditions and disorders. They are also increasingly used by patients themselves for at-home monitoring of such conditions and disorders.
Among the most important of such systems are the "thin layer" systems in which a solvent moves across a thin, flat, absorbent medium. Among the most important of tests that can be performed with such thin layer systems are immunoassays, which depend on the specific interaction between an antigen or a hapten and a corresponding antibody or other specific binding partner.
Among the chromatographic techniques used in conjunction with immunoassays is a procedure known as immunochromatography. In general, this technique uses a disclosing reagent or particle that has been linked to an antibody to the molecule to be assayed, forming a conjugate. This conjugate is then mixed with a specimen, and if the molecule to be assayed is present in the specimen, the disclosing reagent-linked antibodies bind to the molecule to be assayed, thereby giving an indication that the molecule to be assayed is present. The disclosing reagent or particle can be identifiable by color, magnetic properties, radioactivity, specific reactivity with another molecule, enzymatic activity, or another physical or chemical property.
Immunochromatographic assays fall into two principal categories: "sandwich" and "competitive," according to the nature of the antigen-antibody complex to be detected and the sequence of reactions required to produce that complex. The category of assay used is determined by the design of the device, which typically performs a reaction in a specified sequence.
Examples of sandwich immunoassays performed on test strips are described by U.S. Pat. No. 4,168,146 to Grubb et al. and U.S. Pat. No. 4,366,241 to Tom et al., both of which are incorporated herein by this reference.
One particularly useful type of immunochromatographic test device useful for the performance of sandwich and competitive assays employs opposable components and transfers fluid from one opposable component to another during the course of the assay. Typically, such devices employ a precisely calibrated degree of pressure to transfer fluid as desired. Such devices can be constructed in a number of alternative variations.
These devices typically employ a chromatographic medium on one of the opposable components. The other of the opposable components has either a sample application zone or an applicator for applying a detection reagent, which can be a specific binding partner for the analyte or another reagent, depending on the analyte to be detected. In addition, a number of flow patterns are employed within the device.
In one flow pattern, designated "unidirectional," flow occurs along one direction of the chromatographic medium from a first end of the chromatographic medium to a second end of the chromatographic medium. This format is typically used for detection of antigens where a specific antibody exists and the antigen is suitable for assay in a sandwich format. In a second flow pattern, designated "bidirectional," a sample is applied to a first end of the chromatographic medium and traverses the chromatographic medium from its first end to its second end. At this point, the opposable elements are closed, and a detection reagent is applied to the chromatographic medium at or near the second end and traverses the chromatographic medium from the second end to the first end. This assay format is particularly suitable for serological assays in which the analyte is an antibody to a specific antigen and the detection reagent is a second antibody that binds the antibody analyte on the basis of species, class, or subclass specificity.
In a third flow pattern, generally designated "split-flow," the sample is applied to a sample application zone on the opposable element not containing the chromatographic medium, and when the opposable components are brought into operable contact, the sample is applied at a point separated from the ends of the chromatographic medium so that the flow is split, one part of the flow going to the first end and the other part going to the second end.
These differing formats add to the requirements for an improved closure.
Another aspect of these devices that places additional requirements on the closure for such test devices is that it is highly desirable that once closed for the performance of the assay, such devices remain closed and do not inadvertently open. This is particularly important in the light of the increased prevalence of diseases spread by infected blood and blood fractions, such as AIDS and hepatitis. It therefore would be highly desirable to have an improved closure device that can maintain the device in a closed position once the assay has been performed, reducing the risk when the device is disposed.
Additionally, the closure must accommodate varying degrees of pressure as is optimum for each assay format. The internal pressure may be increased if the device incorporates an additional interior component or thicker interior components such as a cotton swab.
One type of closure that has been used in such assay devices is the bevel closure, disclosed in U.S. Pat. No. 5,441,698 to Norell, incorporated herein by this reference. Although the bevel closure has proven useful, after extended use of the bevel closure in a manufactured product, it became apparent that the angle most suitable from a manufacturing standpoint conflicted with angles providing ease of use, i.e. opening and closing of the device, from the customer's perspective. The cut angle providing the most secure closure is consistently more acute than the angle easiest to close.
Thus, there is a need for a closure for use, for example, in testing devices that is relatively simple and inexpensive, and allows the devices to be opened and closed several times without destroying or substantially degrading the performance of the closure, and can apply a closing force evenly between a device flap and a base. Preferably, there is a need to both facilitate the ease of closure and to ensure a secure closure during shelf life up to the point of use and after closure during the performance of the assay to facilitate disposal of the device.